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Published in final edited form as: Ultrasound Med Biol. 2021 Apr 27;47(7):1976–1984. doi: 10.1016/j.ultrasmedbio.2021.03.021

Pre-Operative Femoral Cartilage Ultrasound Characteristics are Altered in People who Report Symptoms at One Year Following Anterior Cruciate Ligament Reconstruction

Matthew S Harkey 1, Jeffrey B Driban 2, Christopher Kuenze 1, Ming Zhang 2,3, Matthew J Salzler 4
PMCID: PMC8169620  NIHMSID: NIHMS1688358  PMID: 33931287

Abstract

We assessed if pre-operative femoral cartilage thickness and echo-intensity on ultrasound are different between participants who were symptomatic (n=6) or asymptomatic (n=7) at 1-year following a primary unilateral anterior cruciate ligament (ACL) reconstruction (age=23±4 years; sex=31% female; BMI=24.9±3.7 kg/m2). A pre-operative, bilateral ultrasound assessment was used to quantify average thickness and echo-intensity in the medial, middle, and lateral femoral trochlear regions. An inter-limb ratio (ACL/Contralateral limb) was calculated for average thickness and echo-intensity. At 1-year following ACL reconstruction, we operationally defined the presence of symptoms as scoring ≤85% on at least two Knee Injury and Osteoarthritis Outcome Score subscales. Independent samples t-tests and Cohen’s d effect sizes were used to compare ultrasound pre-operative inter-limb ratios between participants with and without symptoms at 1-year following ACL reconstruction. For medial femoral cartilage, symptomatic participants had significantly greater average cartilage thickness inter-limb ratios (p=0.01, d=−1.65) and significantly lower echo-intensity inter-limb ratios (p=0.01, d=1.72) when compared to asymptomatic participants. Middle and lateral femoral cartilage average thickness and echo-intensity were not different between the symptomatic and asymptomatic participants. These findings provide preliminary evidence that a clinically feasible ultrasound assessment of the femoral trochlear cartilage may be prognostic of self-reported symptoms at 1-year following ACL reconstruction.

Keywords: knee; ultrasonography; thickness; echo-intensity, echogenicity; KOOS

INTRODUCTION

An estimated 250,000 anterior cruciate ligament (ACL) injuries occur annually in the United States, and this injury is considered one of the strongest risk factors for the development of knee osteoarthritis (OA) (Mall et al. 2014; Silverwood et al. 2015). At a decade following ACL injury or reconstruction, approximately one-third of individuals present with radiographic evidence of knee OA (Luc et al. 2014). Additionally, from 1–6 years after an ACL reconstruction, 26 to 50% of patients report unacceptable symptoms (Ardern et al. 2016; Ingelsrud et al. 2015; Roos et al. 2019). Thus, for some people, an ACL injury is a catalyst that starts them on a trajectory of impaired quality of life and diminished physical function that may lead to long-term psychosocial, economic, and other health implications (Driban et al. 2020; Mather et al. 2013; Meehan et al. 2018). Clinicians need a strategy to identify people early following ACL injury who are at risk for poor self-reported outcomes following reconstruction (Chu et al. 2012) to deliver additional therapies to prevent chronic clinical impairments (Kraus et al. 2012; Lattermann et al. 2017; Risberg et al. 2016; Whittaker et al. 2019).

Since articular cartilage alterations are considered a hallmark sign of knee OA, using imaging modalities to detect early alterations in cartilage may be one option for identifying people at risk for disease development (Chu et al. 2012). Specifically, cartilage alterations commonly occur within the first 12 months following ACL injury or reconstruction (Frobell 2011; Theologis et al. 2014). While most cartilage imaging studies focus on the tibiofemoral joint after an ACL injury, there is evidence that compositional and morphological cartilage alterations are more common in the patellofemoral joint (i.e., femoral trochlea and patella) than the tibiofemoral joint (Culvenor et al. 2015; Culvenor et al. 2016; Culvenor et al. 2013; Culvenor et al. 2016; Culvenor et al. 2019; Frobell 2011; Kim et al. 2018). Furthermore, greater baseline inter-limb differences in femoral trochlear cartilage composition are associated with worse self-reported function at 1-year following ACL reconstruction (Su et al. 2016). Thus, alterations in the femoral trochlear cartilage are prevalent following ACL reconstruction and are prognostic of later poor clinical outcomes. However, previous studies have primarily used magnetic resonance (MR) imaging to assess femoral trochlear cartilage, which is too expensive and inaccessible for common use in the clinic or most research settings (Emery et al. 2019).

Ultrasound has benefits in musculoskeletal medicine and offers a valid, reliable, and clinically-accessible alternative to MR imaging that provides a localized assessment of femoral trochlear cartilage in people following ACL reconstruction (Akkaya et al. 2016; Chang et al. 2020; Chiu et al. 2020; Harkey et al. 2018; Naredo et al. 2009; Pamukoff et al. 2018). In addition to measuring cartilage size, assessing the signal intensity of the ultrasound image (i.e., brightness of the cartilage) is theorized to quantify the integrity of the superficial cartilage collagen matrix (Kuroki et al. 2008). Since disrupted cartilage integrity (e.g., altered cartilage composition) may occur prior to changes in cartilage thickness (Li et al. 2013), an assessment of cartilage ultrasound signal intensity may be an early indicator of cartilage health decline (Gupta et al. 2014; Hiroshi et al. 2008; Pamukoff et al. 2020; Saarakkala et al. 2012). As a non-invasive measure of ultrasound signal intensity, one of our prior reports recently used an in vivo assessment of cartilage ultrasound echo-intensity in people following ACL injury (Harkey et al. 2021). Our results highlighted that people with femoral cartilage damage following an ACL injury – based on an arthroscopic assessment – have lower ultrasound echo-intensity in their femoral trochlear cartilage compared to people without arthroscopic cartilage damage, despite no differences in cartilage thickness (Harkey et al. 2021). While ultrasound-based cartilage assessments hold great promise, there have been no studies to determine the prognostic potential of pre-operative ultrasound characteristics within the femoral trochlear cartilage to differentiate people with and without clinical symptoms following ACL reconstruction.

Therefore, the purpose of this study was to determine if pre-operative trochlear cartilage ultrasound characteristics (i.e., average cartilage thickness and echo-intensity) are different between people with or without symptoms at 1-year following ACL reconstruction. We operationally defined symptom status using criteria established during an international workshop and consensus process that developed a clinical classification of early OA symptoms (Luyten et al. 2018). Specifically, the presence of symptoms was defined as scoring ≤ 85% on at least 2 of 4 Knee Osteoarthritis Outcomes Score (KOOS) subscales. This definition was recently applied to participants following ACL reconstruction (Arhos et al. 2020; Luyten et al. 2018). Based on our prior studies (Harkey et al. 2018; Harkey et al. 2021), we hypothesized that participants with symptoms at 1-year following ACL reconstruction had greater femoral trochlear cartilage thickness and lower echo-intensity than participants without symptoms at 1-year. The results of this preliminary clinical note provide foundational evidence for future studies to establish ultrasound as a prognostic tool to identify people following ACL injury who urgently need additional therapies to improve patient outcomes.

MATERIALS AND METHODS

Participants and Study Design

We performed a prospective cohort study with bilateral femoral cartilage ultrasound assessments at a pre-operative visit and patient-reported symptomatic status defined at 1-year following ACL reconstruction. We recruited participants 18 to 35 years of age prior to undergoing an ACL reconstruction for a primary unilateral ACL injury. A single orthopaedic surgeon (MJS) with a sub-specialty in sports medicine confirmed ACL injury with a clinical knee exam and MR imaging. We excluded participants if they had 1) a history of lower extremity surgery, 2) injured either knee within the prior 6 months (other than ACL injury), 3) multiligament knee injuries, 4) locked bucket-handle meniscal tears, or 5) previously been diagnosed with any form of arthritis. Participants provided written informed consent before data collection, and the university’s Institutional Review Board approved the study.

Ultrasound Assessment of Femoral Trochlea Articular Cartilage

Participant Positioning, Probe Positioning, and Imaging Acquisition

A single examiner (MSH) used a LOGIQ e ultrasound machine with a 12L-RS linear probe (GE Healthcare, Chicago, IL) to acquire the ultrasound images. The examiner has over 6 years of experience using ultrasound to assess femoral trochlear cartilage and has demonstrated excellent intra- and inter-rater reliability (ICC2,k ≥ 0.94) using this technique (Lisee et al. 2020). The ultrasound acquisition parameters were kept consistent between all participants. Prior to a scheduled clinic visit with the study orthopaedic surgeon (MJS), the participants sat for 30 minutes before the ultrasound assessment. We then positioned the participant’s ACL injured limb into maximum knee flexion (≥110°) to visualize the femoral articular cartilage (Figure 1A). The examiner used a handheld goniometer to measure the knee angle during the ultrasound assessment. The ultrasound probe was placed in a transverse suprapatellar approach and rotated until perpendicular to the femoral cartilage surface before capturing an image (Figure 1) (Harkey et al. 2017; Lisee et al. 2020; Naredo et al. 2009). The examiner captured three femoral cartilage ultrasound images using the same procedures. The ultrasound probe was removed from the knee and repositioned before acquiring the next image. The same procedures were used to acquire ultrasound images in the contralateral limb. Since the ACL injured limb may have less range of motion than the contralateral limb, we always assessed the ACL injured limb first. This procedure ensured we could match the maximal knee flexion angle to the contralateral limb (mean ± standard deviation knee angle during ultrasound assessment = 127°±13°).

Figure 1. Ultrasound Assessment of Femoral Trochlear Cartilage.

Figure 1.

A) Participant positioning: participants were positioned with their limb in maximal flexion (≥110°) to allow for visualization of the femoral trochlea cartilage. B) Transparency grid attached to ultrasound machine to ensure consistent probe positioning: after the first ultrasound image was captured, the depth of the medial and lateral femoral condyles on the transparency grid was recorded. C) Positioning of lateral femoral condyle: magnified picture from Figure 1B to demonstrate position of lateral femoral condyle on transparency grid. For each successive image, we confirmed similar depth of the medial and lateral femoral condyles using the transparency grid to ensure consistent probe positioning. D) Standardized femoral trochlear cartilage regions: a semi-automated program automatically separated the manual segmentation of trochlear cartilage into standardized medial, intercondylar, and lateral regions to calculate regional cross-sectional cartilage area (solid lines). E) Average cartilage thickness calculation: the automated program also calculated the length of the cartilage-bone interface (dashed lines) for each region. The average cartilage thickness was calculated as the regional cartilage cross-sectional area divided by the length of the cartilage-bone interface.

Ultrasound Image Processing

We used an established semi-automated technique to divide the manual cartilage segmentation into standardized medial, middle, and lateral femoral trochlear regions (Figure 1D, 1E) (Lisee et al. 2020). Briefly, a single reader performed manual segmentations of the total femoral cartilage cross-sectional area of each ultrasound image using the publicly available ImageJ software (https://imagej.nih.gov/)(Lisee et al. 2020). Next, the segmented cartilage image was exported to a custom MATLAB program (Version 9.2, Mathworks, Natick, MA). This program automatically divided the femoral trochlear cartilage into standardized medial, middle, and lateral cartilage regions (Figure 1D)(Lisee et al. 2020). In brief, the middle cartilage region represented 25% of the cartilage and was centered around the deepest point of the intercondylar notch. The medial cartilage region was defined as the cartilage medial to the middle region, and the lateral cartilage region was defined as the cartilage lateral to the middle region (Lisee et al. 2020). The program also generated 2 measures in each region: average cartilage thickness (i.e., cartilage cross-sectional area divided by the length of the cartilage-bone interface [Figure 1E]) and echo-intensity (i.e., average grey-scale pixel value ranging from black [0] to white [255]). We then calculated an inter-limb ratio for average cartilage thickness and echo-intensity as the ACL injured limb divided by the respective region in the contralateral. Hence, an average thickness inter-limb ratio > 1 indicated thicker cartilage in the ACL injured limb than the contralateral limb. The inter-limb ratios describe alterations in cartilage thickness and echo-intensity in the ACL injured limb normalized to the same region in the contralateral limb (Su et al. 2016). Our main ultrasound measures were inter-limb ratios for average thickness and echo-intensity in each cartilage region.

Operational Definition of Early Clinical OA Symptoms

During a 1-year follow-up appointment with the study orthopaedic surgeon, each participant completed the KOOS self-reported questionnaire (Roos et al. 2003). The KOOS is a knee-specific instrument that evaluates both short- and long-term consequences of a knee injury and consists of 5 subscales: quality of life (KOOS QOL), sport and recreation function (KOOS Sport), pain (KOOS Pain), other symptoms (KOOS Symptom), and activities of daily living function (KOOS ADL) (Roos et al. 2003). We used an established criteria to define clinical OA symptoms that was recently applied to patients following ACL reconstruction (Arhos et al. 2020; Luyten et al. 2018). Specifically, the presence of symptoms at 1-year following ACL reconstruction was operationally defined as a participant scoring ≤ 85% on at least 2 of the following 4 KOOS subscales: QOL, Pain, Symptom, or ADL (Arhos et al. 2020; Luyten et al. 2018).

Statistical Analysis

The 6 dependent variables used in our analyses were pre-operative inter-limb ratios of femoral trochlear cartilage average thickness and echo-intensity in the medial, middle, and lateral regions. The independent variable used in our analysis was the presence (symptomatic group) or absence (asymptomatic group) of clinical symptoms at 1-year following ACL reconstruction, as defined by the composite, dichotomous KOOS variable (Luyten et al. 2018). We used independent samples t-tests to compare the pre-operative inter-limb ultrasound characteristics between participants with and without clinical OA symptoms at 1-year following ACL reconstruction. Additionally, we calculated Cohen’s d effect sizes with 95% confidence intervals (CI) to describe the magnitude of the difference in ultrasound characteristics between the two groups (Parker et al. 2005). Cohen’s d effect sizes are calculated as the mean difference between the symptomatic and asymptomatic participant groups divided by the pooled standard deviation across the groups (Parker et al. 2005). A positive Cohen’s d effect size indicates that the symptomatic group mean is greater than the asymptomatic group, whereas a negative Cohen’s d effect size indicates that the symptomatic group mean is less than the asymptomatic group. Using previously established cut thresholds, we categorized effect sizes as small = 0.20 – 0.49, medium = 0.50 – 0.79, or large = ≥ 0.80 (Parker et al. 2005). All statistical analyses were performed using SAS software, version 9.4 (SAS Institute) with an a priori α level of 0.05.

RESULTS

We included 13 participants with an average age of 23 years who sustained an ACL injury at an average of roughly two months prior to the pre-operative assessment (Table 1). Using the previously established criteria for symptoms (Luyten et al. 2018), there were 6 symptomatic and 7 asymptomatic participants. Means and standard deviations for the 1-year patient-reported outcomes and the pre-operative femoral cartilage ultrasound measures are reported in Tables 1 and 2, respectively.

Table 1.

Participant Characteristics.

All Symptomatic Asymptomatic
Pre-operative Characteristics n (female n) 13 (4) 6 (3) 7 (1)
Body mass index (kg/m2) 24.9 ± 3.7 25.7 ± 4.8 24.3 ± 3.1
Age (years) 23.0 ± 4.1 22.0 ± 4.4 24.0 ± 3.8
Time from injury to surgery (days) 61.9 ± 67.5 40.2 ± 41.3 80.6 ± 82.6
Knee angle during ultrasound assessment (°) 127 ± 13 128 ± 14 126 ± 13
1-year KOOS Scores KOOS QOL 78.4 ± 27.1 57.3 ± 27.2 96.4 ± 4.9
KOOS Pain 92.9 ± 15.3 85.6 ± 21.0 99.2 ± 1.4
KOOS Symptoms 70.1 ± 20.2 56.0 ± 14.0 82.1 ± 16.8
KOOS ADL 96.0 ± 10.4 91.7 ± 14.7 99.8 ± 98.5

mean ± standard deviation unless otherwise noted

Table 2.

Comparing Pre-operative Inter-Limb Ratios in Ultrasound Characteristics between Participants With and Without Symptoms at 1-Year Post-ACL Reconstruction

Pre-operative Ultrasound Measures 1-Year Symptom Status Inter-limb Ratio Cohen’s d 95% CI
N Mean SD t p Lower Upper
Average Thickness Medial Asymptomatic 7 0.95 0.11 −2.96 0.01* −1.65^ −3.03 −0.19
Symptomatic 6 1.13 0.11
Middle Asymptomatic 7 1.01 0.13 −0.80 0.44 −0.45 −1.55 0.69
Symptomatic 6 1.06 0.11
Lateral Asymptomatic 7 1.03 0.13 −0.13 0.90 −0.07 −1.16 1.02
Symptomatic 6 1.04 0.07
Echo-Intensity Medial Asymptomatic 7 1.04 0.04 3.08 0.01* 1.72^ 0.23 3.12
Symptomatic 6 0.96 0.05
Middle Asymptomatic 7 1.00 0.06 0.75 0.47 0.42 −0.72 1.51
Symptomatic 6 0.97 0.09
Lateral Asymptomatic 7 1.01 0.08 0.65 0.53 0.36 −0.76 1.46
Symptomatic 6 0.98 0.10
*

= statistically significant difference in baseline ultrasound measures between participants with and without symptoms at 1 year post-anterior cruciate ligament reconstruction.

^

= effect size indicates large magnitude difference between participants with and without symptoms at 1 year post-anterior cruciate ligament reconstruction.

Differences in Pre-Operative Femoral Cartilage Characteristics between Symptomatic and Asymptomatic Participants at 1-Year Post ACL Reconstruction

For medial femoral cartilage, symptomatic participants had a significantly greater average cartilage thickness inter-limb ratio (i.e., thicker cartilage in ACL reconstructed limb; p=0.01; d [95% CI] =−1.65 [−3.03, −0.19]) and a significantly lower echo-intensity inter-limb ratio (i.e., less bright cartilage appearance in the ACL reconstructed limb; p=0.01; d [95% CI] =1.72 [0.23, 3.12]) when compared to the asymptomatic participants (Table 2). Figure 2 displays box plots with individual participant data points to highlight the difference in medial femoral average cartilage thickness and echo-intensity between the two groups. Middle and lateral femoral cartilage average thickness and echo-intensity was not statistically different between the symptomatic and asymptomatic participants (Table 2).

Figure 2. Boxplots Highlighting the Difference in Femoral Cartilage Average Thickness and Echo-Intensity Inter-Limb Ratio between Participants With and Without Symptoms at 1 Year Post-Anterior Cruciate Ligament Reconstruction.

Figure 2.

A) medial thickness, B) medial echo-intensity, C) middle thickness, D) middle echo-intensity, E) lateral thickness, F) lateral echo-intensity. Knee Osteoarthritis Outcomes Score (KOOS) Cutoff = 2 out of 4 subscales with score of ≤ 85%. * = statistically significant difference in baseline ultrasound measures between participants with and without symptoms at 1 year post-anterior cruciate ligament reconstruction.

DISCUSSION

We found that participants with symptoms at 1-year following ACL reconstruction had thicker and less bright medial femoral trochlear cartilage before surgery in their reconstructed limb relative to their contralateral limb compared to participants who were asymptomatic at 1-year post-ACLR (Table 2, Figure 2). Additionally, there were no pre-operative differences between cartilage thickness or echo-intensity of the middle or lateral trochlear region between the participants with and without symptoms. This study is important as it provides preliminary evidence that a clinically accessible ultrasound assessment of the femoral trochlea cartilage detects differences between participants with and without symptoms at 1-year following ACL reconstruction. These findings highlight that we may be able to use this technique to identify people who need additional therapies to prevent chronic knee-related symptoms.

A critical step needed to prevent knee OA following ACL injury and reconstruction is to identify people at high-risk for future disease development (Chu et al. 2012; Watt et al. 2019). Since pre-operative femoral trochlea cartilage ultrasound thickness and echo-intensity is altered in participants with symptoms at 1-year following ACL reconstruction, this provides preliminary evidence that ultrasound may be able to identify individuals at risk for poor clinical symptoms. Future studies will be needed to develop this as a prognostic outcome and identify potential cutoff values to classify individuals at highest risk of poor outcomes. If we can identify individuals at the highest risk for poor outcomes following ACL reconstruction, we may be able to more effectively target interventions [e.g., intra-articular injections (Kraus et al. 2012; Lattermann et al. 2017), exercise programs (Whittaker et al. 2019), and patient education (Whittaker et al. 2019)] aimed at improving function and maintaining joint health (Chu et al. 2012; Risberg et al. 2016; Watt et al. 2019).

Patellofemoral structural alterations may be an important source of symptoms after ACL injury and reconstruction (Culvenor et al. 2016). Specifically, our results align with previous studies that associate early femoral trochlea alterations with later impairments in various patient-reported outcomes. Previously, worse pre-operative femoral trochlea cartilage composition (i.e., T2 relaxation times) was associated with greater disability during activities of daily living at a year following ACL reconstruction (Su et al. 2016). Additionally, the presence of patellofemoral cartilage lesions at 1-year post surgery predicted worse scores on KOOS subscales at three and five years post ACL reconstruction (Culvenor et al. 2016; Patterson et al. 2020). Similarly, our results provide preliminary evidence that ultrasound thickness and echo-intensity alterations in the femoral trochlea cartilage are different between people with or without symptoms at 1-year following ACL reconstruction. Since ultrasound represents a cost effective and clinically accessible technique that is prognostic of poor outcomes following ACL reconstruction, further work is needed to develop and translate this technique as a tool to accurately identify patients at risk for worse symptoms following ACL reconstruction.

We demonstrated that participants following ACL reconstruction present with thicker cartilage in their reconstructed limb when compared to their contralateral limb, as well as a healthy control limb (Harkey et al. 2018). This increase in cartilage thickness is potentially an early sign of knee OA that is theorized to be due to subtle disruptions in cartilage composition that results in cartilage swelling due to an influx of water content (Buck et al. 2010; Chou et al. 2009; Eckstein et al. 2001; Liess et al. 2002). Similarly, in this study, we observed that symptomatic participants at 1-year following ACL reconstruction are more likely to present with thicker medial femoral trochlear cartilage than their contralateral limb. This study provides interesting preliminary evidence that thicker femoral cartilage in the injured limb may be a predictor of poor patient-reported outcomes following ACL reconstruction. Future studies are needed to confirm these findings in a larger cohort, as well as to determine if this initial cartilage thickening is related to the onset of radiographic and clinically-defined knee OA.

This is one of the few studies to quantify in vivo femoral trochlea cartilage echo-intensity using ultrasound as a measure of cartilage quality (Harkey et al. 2018; Harkey et al. 2020; Pamukoff et al. 2020). However, there is evidence that altered ultrasound signal intensity is related to early declines in cartilage health (Finucci et al. 2015; Möller et al. 2008). Qualitatively, degenerated cartilage samples appear with lower ultrasound echo-intensity (i.e., less bright) than healthy cartilage samples (Saarakkala et al. 2006). Additionally, an invasive arthroscopic ultrasound evaluation performed on people at the time of knee replacement found that lower ultrasound signal intensity was associated with greater arthroscopic cartilage damage (Hiroshi et al. 2008). Following ACL injury, we recently observed lower echo-intensity in the medial femoral trochlea in people with cartilage damage – based on an arthroscopic assessment – than those without cartilage damage (Harkey et al. 2020), even though there were no differences in femoral trochlea cartilage thickness between groups. Collectively, these studies highlight the importance of cartilage echo-intensity. This study provides preliminary data that lesser femoral trochlea cartilage echo-intensity is prognostic of poor outcomes following ACL reconstruction. We theorize that cartilage ultrasound echo-intensity may provide an assessment of “cartilage quality”, similar to the validated metrics of ultrasound-assessed “muscle quality” (Young et al. 2015). However, further work is needed to validate ultrasound echo-intensity against compositional magnetic resonance measures of cartilage composition.

While this study provides preliminary data on the difference in femoral trochlea ultrasound cartilage characteristics between people with and without knee symptoms 1 year after surgery, there are some limitations to discuss. First, the sample size was small, in part due to our inability to collect the 1-year follow-ups on 7 participants due to COVID-19. Our small sample size limits our ability to conduct additional stratified analysis across other important variables like sex or concomitant injury. However, the differences in cartilage ultrasound characteristics between the symptomatic and asymptomatic groups warrant further investigation in future studies. This is one of the first studies to quantify in vivo femoral trochlea cartilage ultrasound echo-intensity (Harkey et al. 2018; Harkey et al. 2020; Pamukoff et al. 2020), and further work is needed to determine the best way to process and interpret this outcome. Specifically, in the muscle ultrasound literature, echo-intensity is normalized using a correction factor based on the amount of subcutaneous fat. However, further work is needed to determine if and what the best strategy is for correcting cartilage ultrasound echo-intensity for overlying subcutaneous fat. This study was limited to a baseline, pre-operative ultrasound assessment to predict future patient-reported outcomes following ACL reconstruction. Thus, further work is needed to better understand the longitudinal alterations in ultrasound cartilage characteristics following ACL reconstruction and determine if an early longitudinal change in these ultrasound measures is related to future outcomes.

In conclusion, this study provides preliminary evidence that a pre-operative ultrasound assessment of medial femoral trochlea cartilage detects differences in thickness and echo-intensity between people with and without symptoms at 1-year following ACL reconstruction. These findings are an essential first step needed to develop ultrasound as a prognostic, clinically accessible modality to identify patients following an ACL injury at the highest risk for future knee OA development.

ROLE OF FUNDING SOURCE

MSH was supported by the National Institutes of Health (grant no. 5 TL1 TR 1454-3). This research was supported in part by generous donations to the Tupper Research Fund at Tufts Medical Center.

Footnotes

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CONFLICT OF INTEREST STATEMENT

The authors have no conflicts of interest to report.

REFERENCES

  1. Akkaya S, Akkaya N, Gungor HR, Agladioglu K, Ok N, Ozcakar L. Sonoelastographic evaluation of the distal femoral cartilage in patients with anterior cruciate ligament reconstruction. Eklem Hastalik. Cerrahisi 2016; 27:2–8. [DOI] [PubMed] [Google Scholar]
  2. Ardern CL, Osterberg A, Sonesson S, Gauffin H, Webster KE, Kvist J. Satisfaction With Knee Function After Primary Anterior Cruciate Ligament Reconstruction Is Associated With Self-Efficacy, Quality of Life, and Returning to the Preinjury Physical Activity. Arthroscopy 2016; 32:1631–38 e3. [DOI] [PubMed] [Google Scholar]
  3. Arhos EK, Thoma LM, Grindem H, Logerstedt D, Risberg MA, Snyder-Mackler L. Association of Quadriceps Strength Symmetry and Surgical Status with Clinical Osteoarthritis 5 Years after Anterior Cruciate Ligament Rupture. Arthritis Care Res. (Hoboken) 2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Buck RJ, Wyman BT, Le Graverand MP, Hudelmaier M, Wirth W, Eckstein F, investigators A. Osteoarthritis may not be a one-way-road of cartilage loss--comparison of spatial patterns of cartilage change between osteoarthritic and healthy knees. Osteoarthritis Cartilage 2010; 18:329–35. [DOI] [PubMed] [Google Scholar]
  5. Chang PH, Chen YJ, Chang KV, Wu WT, Özçakar L. Ultrasound measurements of superficial and deep masticatory muscles in various postures: reliability and influencers. Sci. Rep 2020; 10:14357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chiu YH, Chang KV, Chen IJ, Wu WT, Özçakar L. Utility of sonoelastography for the evaluation of rotator cuff tendon and pertinent disorders: a systematic review and meta-analysis. Eur. Radiol 2020; 30:6663–72. [DOI] [PubMed] [Google Scholar]
  7. Chou MC, Tsai PH, Huang GS, Lee HS, Lee CH, Lin MH, Lin CY, Chung HW. Correlation between the MR T2 value at 4.7 T and relative water content in articular cartilage in experimental osteoarthritis induced by ACL transection. Osteoarthritis Cartilage 2009; 17:441–7. [DOI] [PubMed] [Google Scholar]
  8. Chu CR, Williams AA, Coyle CH, Bowers ME. Early diagnosis to enable early treatment of pre-osteoarthritis. Arthritis Res. Ther 2012; 14:212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Culvenor AG, Collins NJ, Guermazi A, Cook JL, Vicenzino B, Khan KM, Beck N, van Leeuwen J, Crossley KM. Early knee osteoarthritis is evident one year following anterior cruciate ligament reconstruction: a magnetic resonance imaging evaluation. Arthritis Rheumatol 2015; 67:946–55. [DOI] [PubMed] [Google Scholar]
  10. Culvenor AG, Collins NJ, Guermazi A, Cook JL, Vicenzino B, Whitehead TS, Morris HG, Crossley KM. Early Patellofemoral Osteoarthritis Features One Year After Anterior Cruciate Ligament Reconstruction: Symptoms and Quality of Life at Three Years. Arthritis Care Res. (Hoboken) 2016; 68:784–92. [DOI] [PubMed] [Google Scholar]
  11. Culvenor AG, Cook JL, Collins NJ, Crossley KM. Is patellofemoral joint osteoarthritis an under-recognised outcome of anterior cruciate ligament reconstruction? A narrative literature review. Br. J. Sports Med 2013; 47:66–70. [DOI] [PubMed] [Google Scholar]
  12. Culvenor AG, Crossley KM. Patellofemoral Osteoarthritis: Are We Missing an Important Source of Symptoms After Anterior Cruciate Ligament Reconstruction? The Journal of orthopaedic and sports physical therapy 2016; 46:232–4. [DOI] [PubMed] [Google Scholar]
  13. Culvenor AG, Eckstein F, Wirth W, Lohmander LS, Frobell R. Loss of patellofemoral cartilage thickness over 5 years following ACL injury depends on the initial treatment strategy: results from the KANON trial. Br. J. Sports Med 2019; 53:1168–73. [DOI] [PubMed] [Google Scholar]
  14. Driban J, Harkey M, Liu S-H, Salzler M, McAlindon T. Osteoarthritis and Aging: Young Adults with Osteoarthritis. Current Epidemiology Reports 2020:1–7. [Google Scholar]
  15. Eckstein F, Reiser M, Englmeier KH, Putz R. In vivo morphometry and functional analysis of human articular cartilage with quantitative magnetic resonance imaging--from image to data, from data to theory. Anat. Embryol. (Berl.) 2001; 203:147–73. [DOI] [PubMed] [Google Scholar]
  16. Emery CA, Whittaker JL, Mahmoudian A, Lohmander LS, Roos EM, Bennell KL, Toomey CM, Reimer RA, Thompson D, Ronsky JL, Kuntze G, Lloyd DG, Andriacchi T, Englund M, Kraus VB, Losina E, Bierma-Zeinstra S, Runhaar J, Peat G, Luyten FP, Snyder-Mackler L, Risberg MA, Mobasheri A, Guermazi A, Hunter DJ, Arden NK. Establishing outcome measures in early knee osteoarthritis. Nat. Rev. Rheumatol 2019; 15:438–48. [DOI] [PubMed] [Google Scholar]
  17. Finucci A, Iorgoveanu V, Rutigliano IM, Scirocco C, Iagnocco A. Utilizing ultrasound in the diagnosis and management of osteoarthritis. Int. J. Clin. Rheumtol 2015; 10:433–40. [Google Scholar]
  18. Frobell RB. Change in cartilage thickness, posttraumatic bone marrow lesions, and joint fluid volumes after acute ACL disruption: a two-year prospective MRI study of sixty-one subjects. J. Bone Joint Surg. Am 2011; 93:1096–103. [DOI] [PubMed] [Google Scholar]
  19. Gupta R, Virayavanich W, Kuo D, Su F, Link T, Ma B, Li X. MR T(1)rho quantification of cartilage focal lesions in acutely injured knees: correlation with arthroscopic evaluation. Magn. Reson. Imaging 2014; 32:1290–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Harkey MS, Blackburn JT, Davis H, Sierra-Arevalo L, Nissman D, Pietrosimone B. Ultrasonographic assessment of medial femoral cartilage deformation acutely following walking and running. Osteoarthritis Cartilage 2017; 25:907–13. [DOI] [PubMed] [Google Scholar]
  21. Harkey MS, Blackburn JT, Hackney AC, Lewek MD, Schmitz RJ, Nissman D, Pietrosimone B. Comprehensively Assessing the Acute Femoral Cartilage Response and Recovery after Walking and Drop-Landing: An Ultrasonographic Study. Ultrasound Med. Biol 2018; 44:311–20. [DOI] [PubMed] [Google Scholar]
  22. Harkey MS, Blackburn JT, Nissman D, Davis H, Durrington I, Rizk C, Kuismanen A, Pietrosimone B. Ultrasonographic Assessment of Femoral Cartilage in Individuals With Anterior Cruciate Ligament Reconstruction: A Case-Control Study. J Athl Train 2018; 53:1082–88. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Harkey MS, Little E, Thompson M, Zhang M, Driban JB, Salzler MJ. Ultrasound-based cartilage outcomes differentiate healthy and medial femoral cartilage damage after anterior cruciate ligament injury: A preliminary investigation. Osteoarthritis Cartilage 2020; 28:S289–S90. [Google Scholar]
  24. Harkey MS, Little E, Thompson M, Zhang M, Driban JB, Salzler MJ. Femoral Cartilage Ultrasound Echo Intensity Associates with Arthroscopic Cartilage Damage. Ultrasound Med. Biol 2021; 47:43–50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hiroshi K, Yasuaki N, Koji M, Masahiko K, Ko Y, Yukihiro O, Takashi S, Kohei N, Takashi N. Ultrasound properties of articular cartilage in the tibio-femoral joint in knee osteoarthritis: relation to clinical assessment (International Cartilage Repair Society grade). Arthritis Res. Ther 2008; 10:R78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ingelsrud LH, Granan LP, Terwee CB, Engebretsen L, Roos EM. Proportion of Patients Reporting Acceptable Symptoms or Treatment Failure and Their Associated KOOS Values at 6 to 24 Months After Anterior Cruciate Ligament Reconstruction: A Study From the Norwegian Knee Ligament Registry. Am. J. Sports Med 2015; 43:1902–7. [DOI] [PubMed] [Google Scholar]
  27. Kim CW, Hosseini A, Lin L, Wang Y, Torriani M, Gill T, Grodzinsky AJ, Li G. Quantitative analysis of T2 relaxation times of the patellofemoral joint cartilage 3 years after anterior cruciate ligament reconstruction. J Orthop Translat 2018; 12:85–92. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kraus VB, Birmingham J, Stabler TV, Feng S, Taylor DC, Moorman CT 3rd, Garrett WE, Toth AP. Effects of intraarticular IL1-Ra for acute anterior cruciate ligament knee injury: a randomized controlled pilot trial (NCT00332254). Osteoarthritis Cartilage 2012; 20:271–8. [DOI] [PubMed] [Google Scholar]
  29. Kuroki H, Nakagawa Y, Mori K, Kobayashi M, Yasura K, Okamoto Y, Suzuki T, Nishitani K, Nakamura T. Ultrasound properties of articular cartilage in the tibio-femoral joint in knee osteoarthritis: relation to clinical assessment (International Cartilage Repair Society grade). Arthritis Res. Ther 2008; 10:R78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lattermann C, Jacobs CA, Proffitt Bunnell M, Huston LJ, Gammon LG, Johnson DL, Reinke EK, Huebner JL, Kraus VB, Spindler KP. A Multicenter Study of Early Anti-inflammatory Treatment in Patients With Acute Anterior Cruciate Ligament Tear. Am. J. Sports Med 2017; 45:325–33. [DOI] [PubMed] [Google Scholar]
  31. Li X, Majumdar S. Quantitative MRI of articular cartilage and its clinical applications. J. Magn. Reson. Imaging 2013; 38:991–1008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Liess C, Lüsse S, Karger N, Heller M, Glüer CCC. Detection of changes in cartilage water content using MRI T2-mapping in vivo. Osteoarthritis Cartilage 2002; 10:907–13. [DOI] [PubMed] [Google Scholar]
  33. Lisee C, McGrath ML, Kuenze C, Zhang M, Salzler M, Driban JB, Harkey MS. Reliability of a Novel Semiautomated Ultrasound Segmentation Technique for Assessing Average Regional Femoral Articular Cartilage Thickness. J Sport Rehabil 2020; 29:1042–46. [DOI] [PubMed] [Google Scholar]
  34. Luc B, Gribble PA, Pietrosimone BG. Osteoarthritis prevalence following anterior cruciate ligament reconstruction: a systematic review and numbers-needed-to-treat analysis. J Athl Train 2014; 49:806–19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Luyten FP, Bierma-Zeinstra S, Dell’Accio F, Kraus VB, Nakata K, Sekiya I, Arden NK, Lohmander LS. Toward classification criteria for early osteoarthritis of the knee. Semin. Arthritis Rheum 2018; 47:457–63. [DOI] [PubMed] [Google Scholar]
  36. Mall NA, Chalmers PN, Moric M, Tanaka MJ, Cole BJ, Bach BR Jr., Paletta GA Jr. Incidence and trends of anterior cruciate ligament reconstruction in the United States. Am. J. Sports Med 2014; 42:2363–70. [DOI] [PubMed] [Google Scholar]
  37. Mather RC 3rd, Koenig L, Kocher MS, Dall TM, Gallo P, Scott DJ, Bach BR Jr., Spindler KP, Group MK. Societal and economic impact of anterior cruciate ligament tears. J. Bone Joint Surg. Am 2013; 95:1751–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Meehan WP, Weisskopf MG, Krishnan S, McCracken C, Zafonte R, Taylor HA, Baggish A, Pascual-Leone A, Nadler LM, Speizer FE. Relation of Anterior Cruciate Ligament Tears to Potential Chronic Cardiovascular diseases. The American journal of cardiology 2018; 122:1879–84. [DOI] [PubMed] [Google Scholar]
  39. Möller I, Bong D, Naredo E, Filippucci E, Carrasco I, Moragues C, Iagnocco A. Ultrasound in the study and monitoring of osteoarthritis. Osteoarthritis Cartilage 2008; 16:S4–S7. [DOI] [PubMed] [Google Scholar]
  40. Naredo E, Acebes C, Moller I, Canillas F, de Agustin JJ, de Miguel E, Filippucci E, Iagnocco A, Moragues C, Tuneu R, Uson J, Garrido J, Delgado-Baeza E, Saenz-Navarro I. Ultrasound validity in the measurement of knee cartilage thickness. Ann. Rheum. Dis 2009; 68:1322–7. [DOI] [PubMed] [Google Scholar]
  41. Pamukoff DN, Montgomery MM, Moffit TJ, Vakula MN. Quadriceps Function and Knee Joint Ultrasonography after ACL Reconstruction. Med. Sci. Sports Exerc 2018; 50:211–17. [DOI] [PubMed] [Google Scholar]
  42. Pamukoff DN, Vakula MN, Holmes SC, Shumski EJ, Garcia SA. Body mass index moderates the association between gait kinetics, body composition and femoral knee cartilage characteristics. J Orthop Res Official Publ Orthop Res Soc 2020. [DOI] [PubMed] [Google Scholar]
  43. Parker M, Gansneder B. Effect Size: Definition and Application. International Journal of Athletic Therapy and Training 2005; 10:53–55. [Google Scholar]
  44. Patterson BE, Culvenor AG, Barton CJ, Guermazi A, Stefanik JJ, Crossley KM. Patient- Reported Outcomes One to Five Years After Anterior Cruciate Ligament Reconstruction: The Effect of Combined Injury and Associations With Osteoarthritis Features Defined on Magnetic Resonance Imaging. Arthritis Care Res. (Hoboken) 2020; 72:412–22. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Risberg MA, Grindem H, Øiestad BE. We Need to Implement Current Evidence in Early Rehabilitation Programs to Improve Long-Term Outcome After Anterior Cruciate Ligament Injury. The Journal of orthopaedic and sports physical therapy 2016; 46:710–3. [DOI] [PubMed] [Google Scholar]
  46. Roos EM, Boyle E, Frobell RB, Lohmander LS, Ingelsrud LH. It is good to feel better, but better to feel good: whether a patient finds treatment ‘successful’ or not depends on the questions researchers ask. 2019:bjsports-2018–100260. [DOI] [PubMed]
  47. Roos EM, Lohmander LS. The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis. Health Qual Life Outcomes 2003; 1:64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Saarakkala S, Laasanen MS, Jurvelin JS, Toyras J. Quantitative ultrasound imaging detects degenerative changes in articular cartilage surface and subchondral bone. Phys. Med. Biol 2006; 51:5333–46. [DOI] [PubMed] [Google Scholar]
  49. Saarakkala S, Waris P, Waris V, Tarkiainen I, Karvanen E, Aarnio J, Koski JM. Diagnostic performance of knee ultrasonography for detecting degenerative changes of articular cartilage. Osteoarthritis Cartilage 2012; 20:376–81. [DOI] [PubMed] [Google Scholar]
  50. Silverwood V, Blagojevic-Bucknall M, Jinks C, Jordan JL, Protheroe J, Jordan KP. Current evidence on risk factors for knee osteoarthritis in older adults: a systematic review and meta-analysis. Osteoarthritis Cartilage 2015; 23:507–15. [DOI] [PubMed] [Google Scholar]
  51. Su F, Pedoia V, Teng HLL, Kretzschmar M, Lau BC, McCulloch CE, Link TM, Ma CB, Li X. The association between MR T1ρ and T2 of cartilage and patient-reported outcomes after ACL injury and reconstruction. Osteoarthritis Cartilage 2016; 24:1180–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Theologis AA, Haughom B, Liang F, Zhang Y, Majumdar S, Link TM, Ma CB, Li X. Comparison of T1rho relaxation times between ACL-reconstructed knees and contralateral uninjured knees. Knee Surg. Sports Traumatol. Arthrosc 2014; 22:298–307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Watt FE, Corp N, Kingsbury SR, Frobell R, Englund M, Felson DT, Levesque M, Majumdar S, Wilson C, Beard DJ, Lohmander LS, Kraus VB, Roemer F, Conaghan PG, Mason DJ, Arthritis Research UKO, Crystal Disease Clinical Study Group Expert Working G. Towards prevention of post-traumatic osteoarthritis: report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury. Osteoarthritis Cartilage 2019; 27:23–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Whittaker JL, Roos EM. A pragmatic approach to prevent post-traumatic osteoarthritis after sport or exercise-related joint injury. Best Pract. Res. Clin. Rheumatol 2019; 33:158–71. [DOI] [PubMed] [Google Scholar]
  55. Young HJ, Jenkins NT, Zhao Q, McCully KK. Measurement of intramuscular fat by muscle echo intensity. Muscle Nerve 2015; 52:963–71. [DOI] [PMC free article] [PubMed] [Google Scholar]

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